scholarly journals Oxidative Phosphorylation: A Target for Novel Therapeutic Strategies Against Ovarian Cancer

Cancers ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 337 ◽  
Author(s):  
Amruta Nayak ◽  
Arvinder Kapur ◽  
Lisa Barroilhet ◽  
Manish Patankar
Keyword(s):  
Ovarian Cancer ◽  
Oxidative Phosphorylation ◽  
Aerobic Glycolysis ◽  
Ovarian Tumors ◽  
Metabolic Adaptation ◽  
Ovarian Cancer Stem Cells ◽  
Critical Control Points ◽  
Energy Needs ◽  
Oxidative Phosphorylation Pathway ◽  
Novel Therapeutic Strategies

Aerobic glycolysis is an important metabolic adaptation of cancer cells. There is growing evidence that oxidative phosphorylation is also an active metabolic pathway in many tumors, including in high grade serous ovarian cancer. Metastasized ovarian tumors use fatty acids for their energy needs. There is also evidence of ovarian cancer stem cells privileging oxidative phosphorylation (OXPHOS) for their metabolic needs. Metformin and thiazolidinediones such as rosiglitazone restrict tumor growth by inhibiting specific steps in the mitochondrial electron transport chain. These observations suggest that strategies to interfere with oxidative phosphorylation should be considered for the treatment of ovarian tumors. Here, we review the literature that supports this hypothesis and describe potential agents and critical control points in the oxidative phosphorylation pathway that can be targeted using small molecule agents. In this review, we also discuss potential barriers that can reduce the efficacy of the inhibitors of oxidative phosphorylation.

scholarly journals Novel Therapeutic Strategies for Ovarian Cancer Stem Cells

2020 ◽  
Vol 10 ◽  
Author(s):  
Nastassja Terraneo ◽  
Francis Jacob ◽  
Anna Dubrovska ◽  
Jürgen Grünberg
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Therapeutic Strategies ◽  
Ovarian Cancer Stem Cells ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

scholarly journals Platinum (II) Nanofibers as Assembly-driven Inhibitors of Metabolic Adaptation in Cancer Cells

2021 ◽  
Author(s):  
Zhixuan Zhou ◽  
Konrad Maxeiner ◽  
Pierpaolo Moscariello ◽  
Siyuan Xiang ◽  
Yingke Wu ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Histone Deacetylase ◽  
Near Infrared ◽  
Aerobic Glycolysis ◽  
A549 Cells ◽  
Biological Pathways ◽  
Metabolic Adaptation ◽  
Atp Production ◽  
Systemic Level ◽  
Diversity Of Life

Nanostructure-based functions are omnipresent in biology and essential for the diversity of life. Despite their importance, it is difficult to establish mechanisms that define their bioactivity and rationalize them through synthetic designs. As such, strategies that connect bioactive functions through structure formation are scarce. Herein, we design a near-infrared emitting platinum (II)-tripeptide that undergoes a rearrangement using endogenous H2O2 to rapidly assemble into fibrillar superstructures. The resultant assembly inhibits the metabolism of aggressive metastatic MDA-MB-231 cells and A549 cells at the systemic level by blocking aerobic glycolysis and oxidative phosphorylation, thereby shutting down ATP production. Hence, ATP-dependent actin formation and glucose metabolite-dependent histone deacetylase activity are downregulated, leading to apoptosis. By demonstrating that assembly-driven functions can inhibit broad biological pathways, supramolecular nanostructures could offer the next generation biomedical solutions beyond conventional applications.

scholarly journals Targeting IDH1 as a pro-senescent therapy in high-grade serous ovarian cancer

2018 ◽  
Author(s):  
Erika S. Dahl ◽  
Raquel Buj ◽  
Kelly E. Leon ◽  
Jordan M. Newell ◽  
Benjamin G. Bitler ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Aerobic Glycolysis ◽  
Gynecological Cancer ◽  
Significant Proportion ◽  
Tca Cycle ◽  
Metabolic Reprogramming ◽  
Serous Carcinoma ◽  
Metabolic Adaptation ◽  
High Grade ◽  
Novel Therapeutic

AbstractEpithelial ovarian cancer (EOC) is the deadliest gynecological cancer. High-grade serous carcinoma (HGSC) is the most frequently diagnosed and lethal histosubtype of EOC. A significant proportion of HGSC patients relapse with chemoresistant disease. Therefore, there is an urgent need for novel therapeutic strategies for HGSC. Metabolic reprogramming is a hallmark of cancer cells, and targeting metabolism for cancer therapy may be beneficial. Here we found that in comparison to normal fallopian tube epithelial cells, HGSC cells preferentially utilize glucose in the TCA cycle and not for aerobic glycolysis. This correlated with universally increased TCA cycle enzyme expression in HGSC cells under adherent conditions. To further differentiate the necessity of TCA cycle enzymes in ovarian cancer progression, we found that only wildtype isocitrate dehydrogenase I (IDH1) is both significantly increased in HGSC cells in spheroid conditions and is associated with reduced progression-free survival. IDH1 protein expression is also increased in primary HGSC patient tumors. Pharmacological inhibition or knockdown of IDH1 decreased proliferation of multiple HGSC cell lines by inducing senescence. Mechanistically, suppression of IDH1 increased the repressive histone mark H3K9me2 at proliferation promoting gene loci (PCNA and MCM3), which led to decreased mRNA expression. Altogether, these data suggest that increased IDH1 activity is an important metabolic adaptation in HGSC and that targeting wildtype IDH1 in HGSC alters the repressive histone epigenetic landscape to induce senescence. Therefore, inhibition of IDH1 may act as a novel therapeutic approach to alter both the metabolism and epigenetics of HGSC as a pro-senescent therapy.

scholarly journals Fer and FerT Govern Mitochondrial Susceptibility to Metformin and Hypoxic Stress in Colon and Lung Carcinoma Cells

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 97
Author(s):  
Odeya Marciano ◽  
Linoy Mehazri ◽  
Sally Shpungin ◽  
Alexander Varvak ◽  
Eldad Zacksenhaus ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Aerobic Glycolysis ◽  
Metastatic Cancer ◽  
Carcinoma Cells ◽  
Metabolic Adaptation ◽  
Hypoxic Stress ◽  
Lung Carcinoma Cells ◽  
Metabolic Role ◽  
Highly Sensitive ◽  
Anticancer Treatment

Aerobic glycolysis is an important metabolic adaptation of cancer cells. However, there is growing evidence that reprogrammed mitochondria also play an important metabolic role in metastatic dissemination. Two constituents of the reprogrammed mitochondria of cancer cells are the intracellular tyrosine kinase Fer and its cancer- and sperm-specific variant, FerT. Here, we show that Fer and FerT control mitochondrial susceptibility to therapeutic and hypoxic stress in metastatic colon (SW620) and non-small cell lung cancer (NSCLC-H1299) cells. Fer- and FerT-deficient SW620 and H1299 cells (SW∆Fer/FerT and H∆Fer/FerT cells, respectively) become highly sensitive to metformin treatment and to hypoxia under glucose-restrictive conditions. Metformin impaired mitochondrial functioning that was accompanied by ATP deficiency and robust death in SW∆Fer/FerT and H∆Fer/FerT cells compared to the parental SW620 and H1299 cells. Notably, selective knockout of the fer gene without affecting FerT expression reduced sensitivity to metformin and hypoxia seen in SW∆Fer/FerT cells. Thus, Fer and FerT modulate the mitochondrial susceptibility of metastatic cancer cells to hypoxia and metformin. Targeting Fer/FerT may therefore provide a novel anticancer treatment by efficient, selective, and more versatile disruption of mitochondrial function in malignant cells.

scholarly journals The effect of prophylactic bilateral salpingectomy on ovarian reserve in patients who underwent laparoscopic hysterectomy

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Shizhuo Wang ◽  
Jiahui Gu
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Reserve ◽  
Premenopausal Women ◽  
Laparoscopic Hysterectomy ◽  
Ovarian Tumors ◽  
Reproductive Age ◽  
Control Group ◽  
Significant Difference ◽  
Bilateral Salpingectomy ◽  
The Impact

Abstract Background Bilateral salpingectomy has been proposed to reduce the risk of ovarian cancer, but it is not clear whether the surgery affects ovarian reserve. This study compares the impact of laparoscopic hysterectomy for benign disease with or without prophylactic bilateral salpingectomy on ovarian reserve. Methods Records were reviewed for 373 premenopausal women who underwent laparoscopic hysterectomy with ovarian reserve for benign uterine diseases. The serum anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and three-dimensional antral follicle count (AFC) were assessed before surgery and 3 and 9 months postoperatively to evaluate ovarian reserve. Patients were divided into two groups according to whether they underwent prophylactic bilateral salpingectomy. The incidence of pelvic diseases was monitored until the ninth month after surgery. Results There was no significant difference between the two surgery groups in terms of baseline AMH, E2, FSH, LH, and AFC (all P > 0.05). There was no difference in potential bias factors, including patient age, operative time, and blood loss (all P > 0.05). There was also no significant difference between the two groups 3 months after surgery with respect to AMH (P = 0.763), E2 (P = 0.264), FSH (P = 0.478), LH (P = 0.07), and AFC (P = 0.061). Similarly, there were no differences between groups 9 months after surgery for AMH (P = 0.939), E2 (P = 0.137), FSH (P = 0.276), LH (P = 0.07) and AFC (P = 0.066). At 9 months after the operation, no patients had malignant ovarian tumors. The incidences of benign ovarian tumors in the salpingectomy group were 0 and 2.68 % at 3 and 9 months after surgery, respectively, and the corresponding values in the control group were 0 and 5.36 %. The incidences of pelvic inflammatory disease in the salpingectomy group were 10.72 and 8.04 % at 3 and 9 months after surgery, respectively, while corresponding values in the control group were 24.13 and 16.09 %. Conclusions Prophylactic bilateral salpingectomy did not damage the ovarian reserve of reproductive-age women who underwent laparoscopic hysterectomy. Prophylactic bilateral salpingectomy might be a good method to prevent the development of ovarian cancer. Larger clinical trials with longer follow-up times are needed to further evaluate the risks and benefits.

scholarly journals Integrin αvβ3 Engagement Regulates Glucose Metabolism and Migration through Focal Adhesion Kinase (FAK) and Protein Arginine Methyltransferase 5 (PRMT5) in Glioblastoma Cells

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1111
Author(s):  
Pulin Che ◽  
Lei Yu ◽  
Gregory K. Friedman ◽  
Meimei Wang ◽  
Xiaoxue Ke ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Focal Adhesion ◽  
Aerobic Glycolysis ◽  
Integrin Αvβ3 ◽  
Metabolic Reprogramming ◽  
Migration And Invasion ◽  
Metabolic Shift ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Glioblastoma Cells ◽  
Arginine Methyltransferase

Metabolic reprogramming promotes glioblastoma cell migration and invasion. Integrin αvβ3 is one of the major integrin family members in glioblastoma multiforme cell surface mediating interactions with extracellular matrix proteins that are important for glioblastoma progression. The role of αvβ3 integrin in regulating metabolic reprogramming and its mechanism of action have not been determined in glioblastoma cells. Integrin αvβ3 engagement with osteopontin promotes glucose uptake and aerobic glycolysis, while inhibiting mitochondrial oxidative phosphorylation. Blocking or downregulation of integrin αvβ3 inhibits glucose uptake and aerobic glycolysis and promotes mitochondrial oxidative phosphorylation, resulting in decreased migration and growth in glioblastoma cells. Pharmacological inhibition of focal adhesion kinase (FAK) or downregulation of protein arginine methyltransferase 5 (PRMT5) blocks metabolic shift toward glycolysis and inhibits glioblastoma cell migration and invasion. These results support that integrin αvβ3 and osteopontin engagement plays an important role in promoting the metabolic shift toward glycolysis and inhibiting mitochondria oxidative phosphorylation in glioblastoma cells. The metabolic shift in cell energy metabolism is coupled to changes in migration, invasion, and growth, which are mediated by downstream FAK and PRMT5 in glioblastoma cells.

Sign in / Sign up

Export Citation Format

Share Document